Correlation and prediction of gene expression level from amino acid and dipeptide composition of its protein

BACKGROUND: A large number of papers have been published on analysis of microarray data with particular emphasis on normalization of data, detection of differentially expressed genes, clustering of genes and regulatory network. On other hand there are only few studies on relation between expression level and composition of nucleotide/protein sequence, using expression data. There is a need to understand why particular genes/proteins express more in particular conditions. In this study, we analyze 3468 genes of Saccharomyces cerevisiae obtained from Holstege et al., (1998) to understand the relationship between expression level and amino acid composition. RESULTS: We compute the correlation between expression of a gene and amino acid composition of its protein. It was observed that some residues (like Ala, Gly, Arg and Val) have significant positive correlation (r > 0.20) and some other residues (Like Asp, Leu, Asn and Ser) have negative correlation (r < -0.15) with the expression of genes. A significant negative correlation (r = -0.18) was also found between length and gene expression. These observations indicate the relationship between percent composition and gene expression level. Thus, attempts have been made to develop a Support Vector Machine (SVM) based method for predicting the expression level of genes from its protein sequence. In this method the SVM is trained with proteins whose gene expression data is known in a given condition. Then trained SVM is used to predict the gene expression of other proteins of the same organism in the same condition. A correlation coefficient r = 0.70 was obtained between predicted and experimentally determined expression of genes, which improves from r = 0.70 to 0.72 when dipeptide composition was used instead of residue composition. The method was evaluated using 5-fold cross validation test. We also demonstrate that amino acid composition information along with gene expression data can be used for improving the function classification of proteins. CONCLUSION: There is a correlation between gene expression and amino acid composition that can be used to predict the expression level of genes up to a certain extent. A web server based on the above strategy has been developed for calculating the correlation between amino acid composition and gene expression and prediction of expression level . This server will allow users to study the evolution from expression data

Revealing hot tear formation dynamics in Al–Cu alloys with X-ray radiography

Hot tears can arise during the late part of alloy solidification because of the shrinkage of isolated liquid as it turns to solid and may have a catastrophic effect on cast tensile properties. Although there are correlations to suggest alloy hot tear sensitivity to casting conditions, they do not capture the influence of microstructure on tearing, such as second-phase particles or intermetallic compounds (IMCs) commonly present in engineering alloys. We use in situ X-ray radiography to quantify the formation and growth behaviour of hot tears in Al-5Cu and Al-5Cu-1Fe alloys during solidification. An automated hot tear detection, tracking and merging algorithm is developed and applied to reveal the role of Fe-rich IMC particles, typical of recycled alloys, on hot tear behaviour. These defects are termed hot tears here on the basis of their complex, extended inter-connected morphology, distinct from more rounded shrinkage porosity. We also visualise and quantify the velocity of interdendritic flow driven by solidification shrinkage, and estimate the pressure changes due to shrinkage. Hot tearing starts at lower solid fraction when IMCs are present due to reduced interdendritic flow, and hot tear formation is more spatially homogeneous, less clustered and more numerous. We show that the largest, most damaging hot tears form from many merging events, that is enhanced by the presence of IMCs

Does the `Higgs' have Spin Zero?

The Higgs boson is predicted to have spin zero. The ATLAS and CMS experiments have recently reported of an excess of events with mass ~ 125 GeV that has some of the characteristics expected for a Higgs boson. We address the questions whether there is already any evidence that this excess has spin zero, and how this possibility could be confirmed in the near future. The excess observed in the gamma gamma final state could not have spin one, leaving zero and two as open possibilities. We calculate the angular distribution of gamma gamma pairs from the decays of a spin-two boson produced in gluon-gluon collisions, showing that is unique and distinct from the spin-zero case. We also calculate the distributions for lepton pairs that would be produced in the W W* decays of a spin-two boson, which are very different from those in Higgs decays, and note that the kinematics of the event selection used to produce the excess observed in the W W* final state have reduced efficiency for spin two.Comment: 22 pages, 22 figures, Version accepted for publication in JHEP, includes additional plots of dilepton mass distribution

On measurement of top polarization as a probe of ttˉt \bar t production mechanisms at the LHC

In this note we demonstrate the use of top polarization in the study of $t \bar t$ resonances at the LHC, in the possible case where the dynamics implies a non-zero top polarization. As a probe of top polarization we construct an asymmetry in the decay-lepton azimuthal angle distribution (corresponding to the sign of $\cos\phi_\ell$) in the laboratory. The asymmetry is non-vanishing even for a symmetric collider like the LHC, where a positive $z$ axis is not uniquely defined. The angular distribution of the leptons has the advantage of being a faithful top-spin analyzer, unaffected by possible anomalous $tbW$ couplings, to linear order. We study, for purposes of demonstration, the case of a $Z'$ as might exist in the little Higgs models. We identify kinematic cuts which ensure that our asymmetry reflects the polarization in sign and magnitude. We investigate possibilities at the LHC with two energy options: $\sqrt{s} = 14$ TeV and $\sqrt{s} = 7$ TeV, as well as at the Tevatron. At the LHC the model predicts net top quark polarization of the order of a few per cent for $M_{Z'} \simeq 1200$ GeV, being as high as $10$ for a smaller mass of the $Z'$ of $700$ GeV and for the largest allowed coupling in the model, the values being higher for the $7$ TeV option. These polarizations translate to a deviation from the standard-model value of azimuthal asymmetry of up to about $4$ ($7$) for $14$ ($7$) TeV LHC, whereas for the Tevatron, values as high as $12$ are attained. For the $14$ TeV LHC with an integrated luminosity of 10 fb$^{-1}$, these numbers translate into a $3 \sigma$ sensitivity over a large part of the range $500 \lesssim M_{Z'} \lesssim 1500$ GeV.Comment: 28 page, LaTeX, requires JHEP style file, 12 figures. Typos corrected and references adde

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

A high-throughput pipeline for scalable kit-free RNA extraction

An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications

SPECULOOS exoplanet search and its prototype on TRAPPIST

One of the most significant goals of modern science is establishing whether life exists around other suns. The most direct path towards its achievement is the detection and atmospheric characterization of terrestrial exoplanets with potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs), i.e. very-low-mass stars and brown dwarfs with effective temperatures lower than 2700 K, represent a unique opportunity to reach this goal within the next decade. The potential of the transit method for detecting potentially habitable Earth-sized planets around these objects is drastically increased compared to Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby UCD would be amenable for a thorough atmospheric characterization, including the search for possible biosignatures, with near-future facilities such as the James Webb Space Telescope. In this chapter, we first describe the physical properties of UCDs as well as the unique potential they offer for the detection of potentially habitable Earth-sized planets suitable for atmospheric characterization. Then, we present the SPECULOOS ground-based transit survey, that will search for Earth-sized planets transiting the nearest UCDs, as well as its prototype survey on the TRAPPIST telescopes. We conclude by discussing the prospects offered by the recent detection by this prototype survey of a system of seven temperate Earth-sized planets transiting a nearby UCD, TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H. Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure

The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide